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Abstract Background Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. Methods Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. Results An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites—ranging from 65.2% (95% credible interval, 46.3%–79.6%) in Albania to 34.9% (95% credible interval, 20.0%–49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%–27.1%) and human metapneumovirus (range, 6.3%–12.0%) were the next-highest contributors to ALRI hospitalizations. Conclusions We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide.

Background This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. Methods/Design We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. Discussion The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.

Background Respiratory syncytial virus (RSV) is the most commonly identified viral pathogen among young children with acute lower respiratory tract infection. Understanding global RSV epidemiology and risk factors for severe illness in low- and middle-income settings is critical as new vaccine candidates become available. Methods We prospectively enrolled infants aged < 1 year hospitalized with any acute illness from sites in Albania, Jordan, Nicaragua and Philippines during 2015–2017. Standardized parental interviews and medical record review were conducted. Respiratory specimens collected during enrollment were tested for RSV using rRT–PCR. RSV A or B subgroup was determined using a CDC-developed rRT–PCR assay. Very severe RSV illness was defined as requiring ICU admission or supplemental oxygen. Factors potentially associated with severity were assessed using individual logistic regression models to adjust for age and study site. Results Overall, 1,129 (31%) of 3634 enrolled infants had RSV infection. The median age of RSV-positive infants was 2.7 (range: < 1 to 11.9) months, 665 (59%) were male, and 63 (6%) had ≥1 underlying medical condition. RSV subgroup was determined for 1,028 (91%); RSV A and B co-circulated at all sites with alternating predominance by study year (figure). 583 (52%) infants had very severe RSV illness, which was significantly associated with younger age (median: 2.0 vs. 4.3 months; P < 0.01), study site (aOR: Jordan 5.0, Albania 2.9, Philippines 1.2, Nicaragua reference; P < 0.01), birth by cesarean section (aOR: 1.4; 95% CI [CI] 1.0–1.8; P = 0.03), having received ICU care after birth (aOR: 1.6; CI 1.0–2.4; P = 0.03), chronic heart or respiratory tract disease (aOR: 1.9; CI 1.0–3.4; P = 0.04), and a low weight-for-age Z score (aOR: 1.8; CI 1.3–2.7; P < 0.01). RSV subgroup was not associated with severity (aOR: 1.0; CI: 0.7–1.3; P = 0.72). Conclusion RSV was associated with a substantial proportion of acute illness among hospitalized infants in middle-income countries. Subgroups co-circulated across sites and study years with varying predominance and resulted in similar illness severity. Significant comorbidities were uncommon, but factors including younger age, low weight-for-age and chronic heart or respiratory tract disease were associated with more severe illness. Disclosures All authors: No reported disclosures.

The World Health Organization (WHO) declared the current COVID-19 a public health emergency of international concern on January 30, 2020. Countries in the Eastern Mediterranean Region (EMR) have a high vulnerability and variable capacity to respond to outbreaks. Many of these countries addressed the need for increasing capacity in the areas of surveillance and rapid response to public health threats. Moreover, countries addressed the need for communication strategies that direct the public to actions for self- and community protection. This viewpoint article aims to highlight the contribution of the Global Health Development (GHD)/Eastern Mediterranean Public Health Network (EMPHNET) and the EMR’s Field Epidemiology Training Program (FETPs) to prepare for and respond to the current COVID-19 threat. GHD/EMPHNET has the scientific expertise to contribute to elevating the level of country alert and preparedness in the EMR and to provide technical support through health promotion, training and training materials, guidelines, coordination, and communication. The FETPs are currently actively participating in surveillance and screening at the ports of entry, development of communication materials and guidelines, and sharing information to health professionals and the public. However, some countries remain ill-equipped, have poor diagnostic capacity, and are in need of further capacity development in response to public health threats. It is essential that GHD/EMPHNET and FETPs continue building the capacity to respond to COVID-19 and intensify support for preparedness and response to public health emergencies.

•Mothers in Albania, Nicaragua, Philippines, and Jordan completed a survey.•Influenza vaccine is not routinely given in these countries.•Many mothers were unaware of the disease or vaccine.•Perceived safety was an important predictor of vaccine intentions. Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers’ knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers’ intent to vaccinate their child. From 2015 to 2017, infants 0–11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6–11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis. In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample. Intent to vaccinate infants aged 6–11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants.